Extensive research has been conducted for a number of years directed toward the development of compounds capable of treating anxiety in humans that are safer to the user and which exhibit fewer side-effects. For example, several clinically established anxiolytic agents such as the barbituates, meprobamate and the benzodiazepines have numerous side effects such as potential for abuse and addiction or potentialion of the effects of ethanol. The mechanism of action of these compounds is believed to involve the GABA/benzodiazepine receptor complex in humans.
Buspirone is another compound which has been studied for the treatment of anxiety. The literature states that Buspirone interacts with reasonable potency only at the 5-HT1A and dopamine receptors. Alfred Goodman, et al., Goodman and Gilman's The Pharmacological Basis of Therapeutics, 8:482 (1990); Tompkins et al. Research Communications in Psychology, Psychiatry, and Behavior, 5:4, p. 338 (1980).
The compounds employed in the present invention are known compounds taught to be compounds active at the muscarinic receptor. such, the compounds are taught to be useful in treating Alzheimer's disease, dementia, antispasmodics, urology, obstetrics, respiratory tract disorders, tardive dyskinesia, hyperkinesia, Tourette Syndrome, mania, severe painful conditions, and glaucoma. There is no disclosure or suggestion in the patents of using the compounds to treat anxiety.
The art has reported that compounds which act as agonists of the cholinergic muscarinic receptor can actually produce anxiety. See, Risch et al. Psychopharmacol. Bull, 19: 696-698 (1983), Nurnberger et al. Psychiatry RES., 9:191-200 (1983), and Nurnberger et al. Psychopharmacol. Bull., 17:80-82 (1982).
Surprisingly, we have discovered that a group of compounds having muscarinic cholinergic activity can be useful for treating anxiety. The present invention relates to a method of treating anxiety. More specifically, the invention provides a method of treating anxiety in humans using specified compounds. The activity of these compounds is believed to be based on agonist action at the muscarinic cholinergic receptor.
As noted hereinbefore, the compounds employed in the method of the present invention are known. The compounds, methods of preparing the compounds, as well as pharmaceutical formulations containing the compounds, are taught in U.S. Pat. Nos. 4,923,880, 5,110,828, 5,041,436, 5,278,170, 7,177,084, 4,992,436, 5,260,293, 4996,201, 5,066,662, 5,066,665, 5,066,663, 4,988,688, 5,106,853, 5,192,765, 5,041,455, 5,043,345, 5,260,314, 5,310,911, 5,106,851, 5,068,237, 5,318,978, 5,242,927, 5,300,516, 5,089,505, 5,302595, 5,219,871, 5,096,890, 5,164,386, 5,164,514, 5,157,160, 5,217,975, and 5,081,130 herein incorporated by reference.